Abstract: Oligonucleotides are provided which are targeted to nucleic acids encoding human raf and capable of inhibiting raf expression. In preferred embodiments, the oligonucleotides are targeted to mRNA encoding human c-raf or human A-raf. The oligonucleotides may have chemical modifications at one or more positions and may be chimeric oligonucleotides. Methods of inhibiting the expression of human raf using oligonucleotides of the invention are also provided. The present invention further comprises methods of detecting the presence of a raf gene using oligonucleotides of the invention, including methods for specific detection of activated truncated raf. Methods of inhibiting hyperproliferation of cells and methods of treating conditions arising from abnormal raf expression which employ oligonucleotides of the invention are also provided.

Abstract: A class of site-specific DNA cleavage agents comprising a sequence-specific DNA binding protein and a nucleolytic moiety attached thereto at an amino acid that is close to DNA in the specific protein-DNA complex, but that is not close to DNA in the non-specific protein DNA complex. These site-specific DNA cleavage agents cleave DNA at specific DNA recognition sites and have little or no non-specific DNA cleavage activity.